Present microscale and nanoscale manipulators often do not provide adequate mechanisms for one or more various applications, such as manipulating a sample being imaged in an electron microscope, or assembling microscale and nanoscale assemblies. For example, many such manipulators do not provide sufficient positional resolution, or provide limited degrees of freedom during manipulation. Existing manipulators also provide no means for adaptable or modular end effectors, and often require numerous vacuum feedthroughs for power, signal and control lines to be fed into the examination chamber of the electron microscope. Furthermore, existing manipulators may provide limited or no electrical, thermal or other interaction with objects being manipulated, and require extensive and otherwise complicated probe processing/change-out procedures. Existing manipulators, their manufacture and their operation are also not easily integrated with existing manufacturing processes, such as those employed in the manufacture of silicon-based transistor and other microelectronic devices.